Disease activity trajectories in rheumatoid arthritis: a tool for prediction of outcome.

Objective: Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method: For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results: Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion: Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.

Unacceptable pain in the BARFOT inception cohort of patients with rheumatoid arthritis: a long-term study.

Objectives: Pain is the most common and troublesome complaint in rheumatoid arthritis (RA). This study aimed to assess the prevalence and clinical implications of unacceptable pain in an inception cohort of patients with RA. Method: This study followed 477 patients from the BARFOT (Better Anti-Rheumatic FarmacOTherapy) early RA cohort for 15 years. Unacceptable pain was defined as ≥ 40 mm on a visual analogue scale for pain, while tolerable pain denoted no pain or pain below this cut-off, according to the patient acceptable symptom state concept. Results: Unacceptable pain was frequent. At the 15 year follow-up visit, 34% had unacceptable pain. Patients with unacceptable pain had, compared with patients with tolerable pain, significantly more disease activity, worse patient global assessment, and worse function on the Health Assessment Questionnaire and Signals of Functional Impairment, but the degree of joint destruction was similar. Disease-modifying anti-rheumatic drug treatment was similar, but patients with unacceptable pain were more often treated with corticosteroids. At 15 years, patients with unacceptable pain who were in remission (33%) had less inflammation and better function than those not in remission, suggesting the presence of non-inflammatory causes of pain. Conclusions: In this cohort of patients with RA, pain was frequent and severe, with negative effects on experienced health and function. Unacceptable pain was frequent and occurred also in patients in remission, indicating that pain in RA is multifactorial and should always be regarded as an important concern in itself. The cause of pain should be recognized and treated appropriately.

Repair of bone erosions in rheumatoid arthritis: a systematic literature review.

Objective: The aim of this study was to review the literature to identify studies reporting repair of erosions in rheumatoid arthritis (RA).Method: A systematic literature search for publications on the repair of erosions was performed in PubMed and Embase, limited to human adults and published in English. Titles, abstracts, and full reports of articles identified were screened by the first author and verified by the second author.Results: The search yielded 411 publications, of which 33 (20 articles and 13 case reports) suggested repair of erosions in RA. There was heterogeneity in study design and different definitions of repair were used. Twelve articles showed strong evidence of repair, in eight articles repair was probable, and in all 13 case reports repair was evident.Conclusion: Repair of erosions does occur in RA. The definition and frequency of repair vary and the possible clinical relevance is unclear, motivating further studies.

Cone-beam computed tomography, a new low-dose three-dimensional imaging technique for assessment of bone erosions in rheumatoid arthritis: reliability assessment and comparison with conventional radiography - a BARFOT study.

OBJECTIVES: To determine the intra- and inter-observer agreement of erosions detected and scored with cone-beam computed tomography (CBCT) of bones in the hands and feet, and to compare CBCT with conventional radiography (CR) for assessment of bone erosions in patients with long-standing rheumatoid arthritis (RA). METHOD: Thirty patients with long-standing RA from the Better Anti-Rheumatic PharmacOTherapy (BARFOT) cohort were examined with CBCT and CR of hands and feet at their 15 year follow-up. Intra- and inter-class correlation coefficients (ICCs) were calculated. Erosions were analysed with the total rheumatoid arthritis magnetic resonance imaging erosion score (RAMRIS erosion score) for ICCs with CBCT, and with the modified RAMRIS erosion score (RAMRIS-mod.) for the same locations as used in the Sharp van der Heijde score and Sharp van der Heijde erosion score for CR. RESULTS: All 30 patients showed erosions on CBCT and 26 on CR. The ICCs for both intra- and inter-observer reliability were 0.92-0.99. CBCT showed numerically more erosions than CR for all regions compared, although a statistically significant difference was found only for the metacarpophalangeal joints [median number of eroded joints 1.0 (range 0-14) with CBCT and 0.5 (0-13) with CR, p = 0.044]. CONCLUSION: CBCT has high reproducibility and is more sensitive than CR in detecting erosions in this cohort of patients with long-standing RA. CBCT has the potential to become an important tool in the detection and follow-up of erosions in patients with RA.

The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor.

OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are reported to associate with more radiographic progression within the total rheumatoid arthritis (RA) population and anti-citrullinated peptide antibody (ACPA)-negative subgroup. We explored the association of anti-CarP with radiographic progression in RA and aimed to replicate the association and evaluate the added value of anti-CarP antibodies in relation to ACPA and rheumatoid factor (RF). METHODS: 576 Swedish and 628 Dutch patients with RA (2394 and 3247 sets of radiographs, respectively) were longitudinally studied. Replication was restricted to the Swedish patients. In both cohorts, the association of anti-CarP with radiographic progression was determined in strata of patients with similar ACPA and RF status; results of both cohorts were combined in fixed-effect meta-analyses. The net percentage of patients for whom the radiographic progression in 5 years was additionally correctly classified when adding anti-CarP to a model including ACPA and RF was evaluated. RESULTS: Anti-CarP associated with radiographic progression in the total Swedish RA population (beta=1.11 per year, p=8.75×10-13) and in the ACPA-negative subgroup (beta=1.14 per year, p=0.034). Anti-CarP associated with more radiographic progression in the strata of ACPA-positive/RF-negative, ACPA-negative/RF-positive and ACPA-positive/RF-positive patients with RA (respective p values 0.014, 0.019 and 0.0056). A model including ACPA and RF correctly classified 54% and 57% of the patients; adding anti-CarP to this model did not increase these percentages (54% and 56% were correctly classified). CONCLUSIONS: Anti-CarP antibodies associated with more severe radiographic progression in the total and ACPA-negative RA population. Anti-CarP-positivity had a statistically significant additive value to ACPA and RF, but did not improve correct classification of patients.

MRI evidence of persistent joint inflammation and progressive joint damage despite clinical remission during treatment of early rheumatoid arthritis.

OBJECTIVES: To determine the value of magnetic resonance imaging (MRI) of bones and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2 years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids. METHOD: Thirteen patients with early RA were treated according to clinical practice and followed with MRI, radiographs, and Disease Activity Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7, 13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints were assessed for synovitis, bone oedema, and erosions using the RA MRI Score (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method. Radiographs were assessed by the van der Heijde modified Sharp score (SHS). Clinical remission was defined by a DAS28 < 2.6. RESULTS: MRI at baseline detected inflammation in joints and tendons in all patients as well as erosions in 10 out of 13 patients. Over time, the erosion score increased while the synovitis and tenosynovitis scores remained almost unchanged. Bone oedema strongly correlated with synovitis. Synovitis and tenosynovitis correlated well with the erosion score at baseline but not thereafter. The MRI changes showed that joint damage started early and continued in the presence of persistent synovial and tenosynovial inflammation. CONCLUSIONS: The observations made in this small study suggest that the treatment goal of 'clinical remission' should be supplemented by a 'joint remission' goal. To this end, MRI is an appropriate tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

Persistently active disease is common in patients with rheumatoid arthritis, particularly in women: a long-term inception cohort study.

OBJECTIVES: Despite improved treatment strategies for rheumatoid arthritis (RA), some patients do not respond satisfactorily. The aim of this study was to investigate the course and outcome of early RA diagnosed during the 1990s and followed for 8 years with a focus on those who did not respond well to treatment. METHOD: This study included 640 patients (66% women) who were enrolled in the BARFOT (Better Anti-Rheumatic PharmacOTherapy) RA inception cohort between the years 1993 and 1999. The 28-joint count Disease Activity Score (DAS28) < 2.6 criteria were used to assess remission. Persistent disease (PD) was defined as absence of remission at all predefined follow-up visits at 1, 2, 5, and 8 years. Function was assessed by Health Assessment Questionnaire (HAQ) and Signals of Functional Impairment (SOFI) scores and radiological joint damage by the Sharp/van der Heijde score (SHS). RESULTS: Of the 640 patients, 214 (37%) had PD (43% of the women and 25% of the men). Over the 8 years of follow-up, patients with PD had significantly worse mean values for patient's global health measured on a visual analogue scale (VAS patGH), VAS pain, HAQ, SOFI, and SHS compared with those in the non-PD group. Multivariate logistic regression analyses revealed that female gender, current smoking, disease activity at baseline, and absence of remission at 6 months independently predicted PD. CONCLUSIONS: Of the patients who entered the early RA inception cohort, 37% suffered a PD course over 8 years. The consequences of PD with regard to general health, pain, function, and joint damage were considerable. Of note, PD was more common in women than in men.

Predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA): results from a randomized trial.

OBJECTIVES: The aim of this study was to apply a previously published method for evaluating radiographic progression, namely, predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA), to the Swedish pharmacotherapy (SWEFOT) trial. METHOD: In SWEFOT, 487 patients with eRA were given methotrexate (MTX), and non-responders were randomized to group A [triple therapy: MTX+sulfasalazine (SSZ)+hydroxychloroquine (HCQ)] and group B [anti-tumour necrosis factor (anti-TNF) therapy: MTX+infliximab]. Responders continued on MTX. Predicted progression for 343 eligible patients was calculated based on the baseline total Sharp/van der Heijde score (SHS) divided by symptom duration, compared to observed progression at 12 and 24 months. RESULTS: Observed radiographic progression was reduced from predicted by a mean of 50.1% (A), 72.3% (B), and 73.9% (MTX) at 12 months and by 87.2, 89.8, and 87.8% at 24 months, respectively. Among completers, reductions of 56.7% (A) and 76.5% (B) at 12 months and of 91.0% and 96.0% at 24 months, respectively, were observed. At 12 months, there were no significant between-group differences. At 24 months, progression was reduced more in group B than in group A (first quartile difference 8.5% favouring group B) and in MTX [n=316, 89.8% (sd±32.0) vs. 87.2% (±32.2), p=0.021; vs. 87.8% (±27.8), p=0.013, respectively]. CONCLUSIONS: The POPeRA method confirms the original SWEFOT finding in that anti-TNF therapy was statistically marginally superior (2.6%) to triple therapy in preventing radiographic progression at 24 months among initial MTX non-responders. The simulation provided through POPeRA may facilitate comparisons of the relative efficacy of various treatments in preventing radiographic progression.

Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts.

BACKGROUND: Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. OBJECTIVE: To determine the effect of smoking on joint damage progression. METHODS: Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. RESULTS: When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). CONCLUSIONS: This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.

The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of extra-articular disease and predicts radiographic progression of joint destruction over 5 years.

OBJECTIVE: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome. METHODS: In a cohort (n = 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0-448). RESULTS: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression. CONCLUSION: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage.

Distribution of erosions in hands and feet at the time for the diagnosis of RA and during 8-year follow-up.

BACKGROUND: Joint destruction in rheumatoid arthritis (RA) is usually evaluated by radiographs of both hands and feet, while the inflammatory status mostly is evaluated by DAS28 which, however, does not include the feet. OBJECTIVES: To investigate the distribution of erosions in hands and feet in early RA over 8 years and its potential clinical implications. Furthermore, the group of patients never showing erosions has been addressed. METHODS: This study comprises 1041 patients from the BARFOT study of patients with early RA. Radiographs of hands and feet were performed at baseline, 1, 2, 5, and 8 years and evaluated by the Sharp van der Heijde scoring (SHS) method (32 joints in the hands and 12 in the feet). Disease activity was measured by DAS28, SR, CRP, and function with HAQ. RESULTS: In the feet, there were significantly more eroded joints in percent of examined joints than in the hands at all time points. Patients with erosions only in the feet were younger, more often seropositive and smokers. They had significantly lower baseline DAS28, than the patients with erosions only in the hands. The patients without erosions over time were, at diagnosis, significantly younger and less frequently seropositive compared with patients having erosions. CONCLUSIONS: This study highlights the importance of evaluating the feet in patients with RA, both with clinical examinations and with imaging and lends support to the notion that seropositivity and smoking are risk factors for erosive disease. Further studies of patients with nonerosive disease are needed. KEY POINTS: • Foot problems are common in RA • This study emphasizes the limitations of DAS28 and Sharp van der Heijde score as regards evaluating disease activity and radiographic damage • This study highlights the importance of evaluating the feet in patients with RA with clinical examinations and imaging • This study also points out the need of further studies of patients with non-erosive RA.

Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial.

BACKGROUND: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis. METHODS: We undertook a randomised trial in 15 rheumatology units in Sweden. We enrolled patients with early rheumatoid arthritis (symptom duration <1 year) and administered methotrexate (up to 20 mg per week). After 3-4 months, those who had not achieved low disease activity but who could tolerate methotrexate were randomly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab. Primary outcome was achievement of a good response according to European League Against Rheumatism (EULAR) criteria at 12 months. Patients were followed up to 24 months; here, we present findings at 12 months. Analysis was by intention to treat and we used non-responder imputation. The Swefot (Swedish Pharmacotherapy) study is registered in the WHO database at the Karolinska University Hospital, number CT20080004. FINDINGS: 487 patients were initially enrolled. Of 258 who had not achieved low disease activity with methotrexate, 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab. 32 of 130 (25%) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 (39%) assigned infliximab (risk ratio 1.59 [95% CI 1.10-2.30], p=0.0160). Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used. No deaths occurred in either group. INTERPRETATION: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. FUNDING: Swedish Rheumatism Association, Schering-Plough.

Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage.

OBJECTIVE: To evaluate gender differences in score on 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and Signals Of Functional Impairment (SOFI) and to relate these scores to radiographic joint destruction. METHODS: In all, 549 patients with early RA (62% women) from the BARFOT (for "Better Anti-Rheumatic FarmacOTherapy") study were included. At baseline, 1, 2 and 5 years DAS28, HAQ and SOFI scoring, and radiographs of hands and feet were performed. The radiographs were scored using the van der Heijde-Sharp score. RESULTS: In women the DAS28 was significantly higher than in men due to higher scores for general health and tender joints. Likewise, HAQ and VAS pain were rated significantly higher in women. The SOFI score was worse in men during the first 2 years, depending on higher upper limb scores. Total Sharp score (TotSharp), erosion score and joint space narrowing score did not differ between the sexes at any time point. The DAS28 area under the curve (AUC) correlated significantly with TotSharp at 5 years in both genders (r = 0.316, r = 0.313) mainly owing to swollen joints and erythrocyte sedimentation rate (ESR). The SOFI AUC correlated significantly with TotSharp in women (r = 0.135 to 0.220) but not in men. CONCLUSIONS: Despite a similar degree of radiographic joint destruction women had, compared with men, worse scores for DAS28 and HAQ, possibly due to higher pain perception and less muscular strength and perhaps because men overestimate their functional capacity.

Hand bone loss measured by digital X-ray radiogrammetry is a predictor of joint damage in early rheumatoid arthritis.

OBJECTIVE: The aim of this study was to evaluate whether loss of bone measured by digital X-ray radiogrammetry (DXR) of hands early in the course of rheumatoid arthritis (RA) may predict future radiographic joint damage after 1 and 2 years. METHODS: A total of 166 patients with early RA, who were part of the Better Anti-Rheumatic FarmacOTherapy (BARFOT) low-dose prednisolone study, were included. The patients had been randomized to treatment with 7.5 mg prednisolone daily or no prednisolone when they started with their first disease-modifying anti-rheumatic drug (DMARD) therapy. Radiographs of hands and feet were taken at baseline and after 1 and 2 years and assessed by the van der Heijde modified Sharp (vdH-S) score. Hand bone density (HBD) was measured on the same radiographs by DXR. Changes in HBD and hand bone loss (HBL) were calculated. HBL was defined as a change in DXR bone mineral density (DXR-BMD) during the first year by more than 0.0048 g/cm(2). RESULTS: HBL was found in 64% of the patients. Patients with HBL had radiological progression significantly more often than patients without (80% vs. 57%, p=0.012). Patients not treated with prednisolone had HBL more often than patients with this treatment (83% vs. 44%, p=0.001). In multiple regression analyses, HBL and change in DXR-BMD during the first year proved to be independent predictors of radiological progression. CONCLUSIONS: Loss of bone measured by DXR was found to be an independent predictor of radiological joint damage and may thus be an additional tool in the process of treatment decision in early RA.

Treatment of early RA in clinical practice: a comparative study of two different DMARD/corticosteroid options.

OBJECTIVES: To study the outcome in clinical practice of first DMARD and/or corticosteroid (CS) treatment in patients with recent onset rheumatoid arthritis (RA). PATIENTS: 245 patients with active RA, not previously treated with DMARDs or CS, were randomised to one of two treatment groups, T1 = 7.5-15 mg of prednisolone (PRE) daily for one to three months followed, if needed, by methotrexate (MTX) in a weekly dose of 5-15 mg in addition to the lowest possible dose of PRE or T2 = sulfasalazine (SAL), supplemented with lowest possible CS dose if needed. METHODS: The EULAR individual response criteria were applied and remission was defined as a final DAS28 < 2.6. Function was assessed by the HAQ and radiographic progression by Larsen scores. A patient who managed to remain on the allocated treatment for two years was described as a "completer". RESULTS: After 2 years of treatment, 70% of the patients in T1 and 63% in T2 were responders (30% and 33% "good responders", respectively). In T1 29% and in T2 19% were in remission. There was a significant functional improvement in both groups but radiographic progression occurred. The mean decrease in HAQ and increase in the Larsen score were similar in the two groups. One-third of the patients were non-completers, 19% from T1 and 47% from T2. Non-completers had, compared with completers, a significantly lower rate of individual response and remission. Completers and non-completers had similar functional improvement and similar radiological progression. CONCLUSIONS: Individual response and remission was reduced in patients who did not complete their first DMARD/CS treatment option. Treatment failures were significantly more frequent in the sulfasalazine plus optional CS than in the CS plus optional methotrexate treatment group.

Alkaptonuria and ochronosis in three siblings. Ascorbic acid treatment monitored by urinary HGA excretion.

Patients with alkaptonuria lack homogentisate 1,2-dioxygenase leading to retention of homogentistic acid (HGA) in body fluids and eventually to tissue deposition of oxidation products, giving rise to the clinical picture of ochronosis. Ascorbic acid is a known inhibitor of the enzyme which catalyses the oxidation of homogentisic acid (HGA) to the polymer with affinity for collagen and was used in the treatment of three siblings with alkaptonuria. Ascorbic acid 500 mg bid was administered for 12 months. Two of the siblings tolerated the treatment, and in one the symptoms improved, whereas in the other they worsened. Plasma and urinary levels of HGA were monitored with a new HPLC method. Ascorbic acid is not effective in the treatment of symptomatic ochronosis.

Sex: a major predictor of remission in early rheumatoid arthritis?

BACKGROUND: The treatment goal of early rheumatoid arthritis is remission. This study reports remission rates in clinical practice using a cohort of patients with early rheumatoid arthritis. METHODS: 698 patients with early rheumatoid arthritis were included. Mean age at inclusion was 58 years and mean disease duration was 6.4 months; 64% of the patients were women, 56% were positive for antibodies to cyclic citrullinated peptide and 60% were positive for rheumatoid factor. Remission was defined as a disease activity score <2.6, with or without ongoing treatment with drugs for rheumatoid arthritis. RESULTS: After 2 years, 261 of 689 patients were in remission (37.9%), and after 5 years, the remission rate was 38.5%. However, only 26.1% were in remission at both these time points. Multiple logistic regression analyses found sex to be a main predictor for remission. Thus, significantly fewer women were in remission after 2 years (32.1% v 48%, p = 0.001) after 5 years (30.8% v 52.4%, p = 0.001) and at both these time points (19.1% v 39.3%, p = 0.001). Although disease activity was not with certainty more pronounced in women at onset of disease, the disease course became markedly worse in women. The disparity in remission frequency between women and men could not be explained by differences in disease duration, age or treatment with disease modifying antirheumatic drugs or glucocorticoids. CONCLUSIONS: Early remission of rheumatoid arthritis by 28-joint Disease Activity Score<2.6 was as frequent or more frequent in this study than in most previous reports. Importantly, women had more severe disease with a considerably lower remission rate than men, although the disease activity before treatment seemed similar.